Nemaline myopathies: a current view
| Autor: | J. Laitila, Carina Wallgren-Pettersson, Caroline Sewry |
|---|---|
| Přispěvatelé: | Katarina Pelin / Principal Investigator, Medicum, Department of Medical and Clinical Genetics, University of Helsinki, University Management, University of Helsinki, Katarina Pelin / Principal Investigator, University of Helsinki, Medicum |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology EXON 55 Physiology FOUNDER MUTATION Muscle Proteins Myopathies Nemaline Biochemistry Rods 0302 clinical medicine Nemaline myopathy Rod bodies Age of Onset GENOTYPE-PHENOTYPE CORRELATIONS Congenital myopathy Z line biology HYPERTROPHIC CARDIOMYOPATHY Microfilament Proteins MOUSE MODEL Phenotype Hypotonia 3. Good health Animal models SKELETAL-MUSCLE Z disc medicine.symptom Sarcomeres medicine.medical_specialty NEBULIN GENE MICE LACKING Article INTRANUCLEAR RODS 03 medical and health sciences Nebulin medicine Humans Myopathy Nemaline bodies Muscle weakness Cell Biology medicine.disease Actins BODY MYOPATHY 030104 developmental biology Mutation biology.protein 1182 Biochemistry cell and molecular biology 3111 Biomedicine 030217 neurology & neurosurgery |
| Zdroj: | Journal of Muscle Research and Cell Motility |
| Popis: | Nemaline myopathies are a heterogenous group of congenital myopathies caused by de novo, dominantly or recessively inherited mutations in at least twelve genes. The genes encoding skeletal α-actin (ACTA1) and nebulin (NEB) are the commonest genetic cause. Most patients have congenital onset characterized by muscle weakness and hypotonia, but the spectrum of clinical phenotypes is broad, ranging from severe neonatal presentations to onset of a milder disorder in childhood. Most patients with adult onset have an autoimmune-related myopathy with a progressive course. The wide application of massively parallel sequencing methods is increasing the number of known causative genes and broadening the range of clinical phenotypes. Nemaline myopathies are identified by the presence of structures that are rod-like or ovoid in shape with electron microscopy, and with light microscopy stain red with the modified Gömöri trichrome technique. These rods or nemaline bodies are derived from Z lines (also known as Z discs or Z disks) and have a similar lattice structure and protein content. Their shape in patients with mutations in KLHL40 and LMOD3 is distinctive and can be useful for diagnosis. The number and distribution of nemaline bodies varies between fibres and different muscles but does not correlate with severity or prognosis. Additional pathological features such as caps, cores and fibre type disproportion are associated with the same genes as those known to cause the presence of rods. Animal models are advancing the understanding of the effects of various mutations in different genes and paving the way for the development of therapies, which at present only manage symptoms and are aimed at maintaining muscle strength, joint mobility, ambulation, respiration and independence in the activities of daily living. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|